Need for nephrectomy challenged in some sunitinib-treated metastatic renal cancers

medwireNews: Results of the phase III CARMENA trial show that treatment with sunitinib alone is as good as treatment with nephrectomy followed by sunitinib in patients with intermediate- or poor-risk metastatic renal cell carcinoma.

“These findings contrast with those of previous retrospective and database studies, which suggested an overall survival benefit with nephrectomy in patients treated with targeted therapies,” write Bernard Escudier (Gustave Roussy Institute, Villejuif, France) and co-authors in The New England Journal of Medicine.

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This may be because patients who undergo nephrectomy typically have more favorable clinical characteristics than those who are not selected for surgery, which could contribute to survival differences observed in retrospective analyses, the researchers remark.

In the CARMENA trial, 450 patients (median age 62 years, 75% men) with metastatic clear-cell renal cell carcinoma who were candidates for nephrectomy were randomly assigned to receive nephrectomy followed by sunitinib 50 mg daily for 28 days of each 6-week cycle or to receive sunitinib alone.

According to the Memorial Sloan Kettering Cancer Center prognostic model, 43% of the patients had poor-risk disease (≥three prognostic factors), while the remainder had intermediate-risk disease (one or two prognostic factors).

During a median follow-up period of 50.9 months, 326 patients died. Median overall survival was 13.9 months in the nephrectomy–sunitinib group and 18.4 months in the sunitinib-alone group.

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Statistical analysis showed that treatment with sunitinib alone was noninferior to treatment with nephrectomy followed by sunitinib when considering overall survival, with a stratified hazard ratio (HR) for death of 0.89.

And this was true for both the 225 patients with an intermediate risk prognosis and the 224 patients with a high-risk prognosis, with HRs for death in the sunitinib-alone versus surgery plus sunitinib arms of 0.92 and 0.86, respectively.

There were also no significant differences between the nephrectomy–sunitinib and sunitinib-alone groups for objective response rate (27.4 vs 29.1%) or median progression-free survival (7.2 vs 8.3 months).

Writing in an accompanying editorial, Robert Motzer and Paul Russo, both from the Memorial Sloan Kettering Cancer Center in New York, USA, point out that “[t]he CARMENA trial was heavily weighted toward poor-risk patients, and it is not surprising that the noninferiority end point was achieved.”

“For practicing surgeons and medical oncologists, these data should not lead to the abandonment of nephrectomy but instead emphasize the importance of careful selection of patients undergoing nephrectomy, on the basis of published risk models,” they add.